The proposed five-year K23 Mentored Patient-Oriented Research Career Development Award outlines a program of career development and research activities that will assist the principal investigator to transition to an independent research career and prepare her to tackle the challenges ahead in unraveling the genetic basis of complex psychiatric phenotypes. The innovative research plan details an approach to mapping risk for a strongly genetic subtype of obsessive compulsive (OCD) and comorbid tic disorders by generating and analyzing whole-exome sequence in select families to identify risk alleles. These efforts will be guided by pilot identity-by-descent, homozygosity, and copy number variant data in the comprehensively phenotyped OCD Collaborative Genetic Study (OCGS) multiplex family dataset. The OCD+tic phenotype is an ideal complex disorder for next generation genetic mapping. The clear phenotype, possibly reduced heterogeneity, and strong genetic effects make it an excellent candidate for the application of methodologies recently proven successful in Mendelian disorders. While the principle investigator has a strong background in child psychiatry and molecular genetics, the knowledge and skills required to master emerging genetic technologies such as next generation sequencing (NGS) are novel and complex. The short-term goals of this application are to gain proficiency in the methods that will drive the field over the coming decades, learn the statistical, computational, and informatics tools that will support this research, continue to develop skills in study design and interpretation, and refine and incorporate clinical and phenotyping skills. A program of coursework, supervision, and hands-on application of these approaches will equip the applicant in the long-term to integrate molecular, computational, and phenotypic data to make meaningful contributions to the field of psychiatric genetics. This award will help the candidate to establish an independent research career, position herself on the front of these new advances, and bring the lessons learned to the field of child psychiatry. PUBLIC HEALTH RELEVANCE: The proposed five-year K23 Mentored Patient-Oriented Research Career Development Award outlines a program of career development and research activities that will assist the principal investigator to transition to an independent research career and prepare her to tackle the challenges ahead in unraveling the genetic basis of complex psychiatric traits. The innovative research plan details an approach to finding risk genes for a strongly genetic subtype of obsessive compulsive (OCD) and comorbid tic disorders by analyzing the full protein-coding sequence of the genome in select families of the comprehensively characterized OCD Collaborative Genetic Study (OCGS). A program of coursework, supervision, and hands-on application of these approaches will equip the applicant in the long-term to integrate molecular, computational, and clinical data to make meaningful contributions to the field of psychiatric genetics.